Position 2: Transarterial Radioembolization Should Be the Primary Locoregional Therapy for Unresectable Hepatocellular Carcinoma.

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-2-reading-rahman a video presentation of this article.

Imaging surveillance and multidisciplinary review improves curative therapy access and survival in HCC patients.

INTRODUCTION: Imaging surveillance and multidisciplinary conference (MDC) review can potentially improve survival in patients with hepatocellular carcinoma (HCC) by increasing access to liver transplantation. Geographic disparities in donor organ availability may reduce this benefit. This study evaluated the impact of HCC surveillance on use of curative therapies and survival in a region with long transplant waiting times. MATERIAL AND METHODS: 167 HCC patients were retrospectively studied. Subjects had an established HCC diagnosis or were diagnosed during hepatology follow-up. Collected data included patient demographics, HCC surveillance and MDC review status, portal hypertension complications, laboratory and radiologic parameters, tumor size, therapeutic interventions, tumor progression, and mortality. The primary outcome measures were use of curative treatments and survival. A Cox-regression model was constructed utilizing factors associated with survival in univariate analysis. RESULTS: 58% of subjects underwent surveillance and MDC review of HCC. These patients were more likely to have received treatment with ablation or resection (16 vs. 3%, P = 0.006) and transplantation (23 vs. 4%, P = 0.001), and were less likely to develop tumor progression (45 vs. 68%, P = 0.005) or metastases (0 vs. 19%, P < 0.001). In multivariate analysis, surveillance and MDC review (P = 0.034, HR 0.520, 95% CI 0.284-0.952), tumor meeting Milan criteria (P < 0.001, HR 0.329, 95% CI 0.178-0.607), curative therapy application (P = 0.048, HR 0.130, 95% CI 0.017-0.979), and transplantation (P = 0.004, HR 0.236, 95% CI 0.088-0.632) were associated with survival. CONCLUSION: In conclusion, imaging surveillance and MDC review is associated with detection of early stage HCC, increased access to curative therapies and transplantation, and prolonged survival.

Physical activity and metabolic syndrome in liver transplant recipients.

There is a high prevalence of metabolic syndrome in liver transplant recipients, a population that tends to be physically inactive. The aim of this study was to characterize physical activity and evaluate the relationship between physical activity and metabolic syndrome after liver transplantation. A cross-sectional analysis was performed in patients more than 3 months after transplantation. Metabolic syndrome was classified according to National Cholesterol Education Panel Adult Treatment Panel III guidelines. Physical activity, including duration, frequency, and metabolic equivalents of task (METs), was assessed. The study population consisted of 204 subjects, with 156 more than 1 year after transplantation. The median time after transplantation was 53.5 months (range = 3-299 months). The mean duration of exercise was 90 ± 142 minutes, and the mean MET score was 3.6 ± 1.5. Metabolic syndrome was observed in 58.8% of all subjects and in 63.5% of the subjects more than 1 year after transplantation. In a multivariate analysis involving all subjects, metabolic syndrome was associated with a time after transplantation greater than 1 year [odds ratio (OR) = 2.909, 95% confidence interval (CI) = 1.389-6.092] and older age (OR = 1.036, 95% CI = 1.001-1.072). A second analysis was performed for only patients more than 1 year after transplantation. In a multivariate analysis, metabolic syndrome was associated with lower exercise intensity (OR = 0.690, 95% CI = 0.536-0.887), older age (OR = 1.056, 95% CI = 1.014-1.101), and pretransplant diabetes (OR = 4.246, 95% CI = 1.300-13.864). In conclusion, metabolic syndrome is common after liver transplantation, and the rate is significantly higher in patients more than 1 year after transplantation. The observation that exercise intensity is inversely related to metabolic syndrome after transplantation is novel and suggests that physical activity might provide a means for reducing metabolic syndrome complications in liver transplant recipients.

Prognostic capability of different liver disease scoring systems for prediction of early mortality after transjugular intrahepatic portosystemic shunt creation.

PURPOSE: To compare the performance of various liver disease scoring systems in predicting early mortality after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: In this single-institution retrospective study, eight scoring systems were used to grade liver disease in 211 patients (male-to-female ratio = 131:80; mean age, 54 y) before TIPS creation from 1999-2011. Scoring systems included bilirubin level, Child-Pugh (CP) score, Model for End-Stage Liver Disease (MELD) and Model for End-Stage Liver Disease sodium (MELD-Na) score, Emory score, prognostic index (PI), Acute Physiology and Chronic Health Evaluation (APACHE) 2 score, and Bonn TIPS early mortality (BOTEM) score. Medical record review was used to identify 30-day and 90-day clinical outcomes. The relationship of scoring parameters with mortality outcomes was assessed with multivariate analysis, and the relative ability of systems to predict mortality after TIPS creation was evaluated by comparing area under receiver operating characteristic (AUROC) curves. RESULTS: TIPS were successfully created for variceal hemorrhage (n = 121), ascites (n = 72), hepatic hydrothorax (n = 15), and portal vein thrombosis (n = 3). All scoring systems had a significant association with 30-day and 90-day mortality (P<.050 in each case) on multivariate analysis. Based on 30-day and 90-day AUROC, MELD (0.878, 0.816) and MELD-Na (0.863, 0.823) scores had the best capability to predict early mortality compared with bilirubin (0.786, 0.749), CP (0.822, 0.771), Emory (0.786, 0.681), PI (0.854, 0.760), APACHE 2 (0.836, 0.735), and BOTEM (0.798, 0.698), with statistical superiority over bilirubin, Emory, and BOTEM scores. CONCLUSIONS: Several liver disease scoring systems have prognostic value for early mortality after TIPS creation. MELD and MELD-Na scores most effectively predict survival after TIPS creation.

Quantitative morphometric analysis of hepatocellular carcinoma: development of a programmed algorithm and preliminary application.

PURPOSE: The quantitative relationship between tumor morphology and malignant potential has not been explored in liver tumors. We designed a computer algorithm to analyze shape features of hepatocellular carcinoma (HCC) and tested feasibility of morphologic analysis. MATERIALS AND METHODS: Cross-sectional images from 118 patients diagnosed with HCC between 2007 and 2010 were extracted at the widest index tumor diameter. The tumor margins were outlined, and point coordinates were input into a MATLAB (MathWorks Inc., Natick, Massachusetts, USA) algorithm. Twelve shape descriptors were calculated per tumor: the compactness, the mean radial distance (MRD), the RD standard deviation (RDSD), the RD area ratio (RDAR), the zero crossings, entropy, the mean Feret diameter (MFD), the Feret ratio, the convex hull area (CHA) and perimeter (CHP) ratios, the elliptic compactness (EC), and the elliptic irregularity (EI). The parameters were correlated with the levels of alpha-fetoprotein (AFP) as an indicator of tumor aggressiveness. RESULTS: The quantitative morphometric analysis was technically successful in all cases. The mean parameters were as follows: compactness 0.88±0.086, MRD 0.83±0.056, RDSD 0.087±0.037, RDAR 0.045±0.023, zero crossings 6±2.2, entropy 1.43±0.16, MFD 4.40±3.14 cm, Feret ratio 0.78±0.089, CHA 0.98±0.027, CHP 0.98±0.030, EC 0.95±0.043, and EI 0.95±0.023. MFD and RDAR provided the widest value range for the best shape discrimination. The larger tumors were less compact, more concave, and less ellipsoid than the smaller tumors (P < 0.0001). AFP-producing tumors displayed greater morphologic irregularity based on several parameters, including compactness, MRD, RDSD, RDAR, entropy, and EI (P < 0.05 for all). CONCLUSION: Computerized HCC image analysis using shape descriptors is technically feasible. Aggressively growing tumors have wider diameters and more irregular margins. Future studies will determine further clinical applications for this morphologic analysis.

Ethnicity and body mass index are associated with hepatitis C presentation and progression.

BACKGROUND & AIMS: Ethnicity and the metabolic syndrome are believed to affect progression of hepatitis C virus (HCV) infection, but the interaction between these factors is unknown. We evaluated the association between elements of the metabolic syndrome and ethnicity in the histologic progression of HCV in a large, diverse cohort. METHODS: We retrospectively evaluated clinical data and liver biopsy samples from 812 patients who had no cause of liver disease other than HCV infection. Liver biopsies were scored for steatosis, necroinflammatory activity, and fibrosis. For each patient with a known risk factor for viral acquisition, fibrosis index was calculated as an indicator of disease progression. RESULTS: Hispanics had significantly higher fibrosis index (0.13 +/- 0.09) than non-Hispanic whites (0.11 +/- 0.07) and African Americans (0.10 +/- 0.06; P = .001). Fibrosis index correlated with body mass index (BMI), older age at infection, ethnicity, and degree of steatosis. Cirrhosis was present in 50% of Hispanics, 38% of non-Hispanic whites, and 24% of African Americans (P < .001). The presence of cirrhosis was associated additionally with older age, longer duration of infection, BMI, alcohol consumption, and diabetes. In multivariate analysis, only BMI and ethnicity were associated with both fibrosis index and presentation with cirrhosis. Patients with higher BMIs, diabetes mellitus, and steatosis had higher degrees of necroinflammation. CONCLUSIONS: Ethnicity and BMI each were associated with the progression of fibrosis and the presence of cirrhosis. Hispanics had the highest fibrosis index and prevalence of cirrhosis, whereas African Americans had the lowest. Ethnic differences in fibrosis index and cirrhosis persisted after controlling for elements of metabolic syndrome.

The histologic spectrum of liver disease in African-American, non-Hispanic white, and Hispanic obesity surgery patients.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a prominent cause of chronic liver disease in African Americans, non-Hispanic whites, and Hispanics. The aim of this study was to evaluate ethnic differences in the prevalence of NAFLD and non-alcoholic steatohepatitis (NASH) and to compare the severity of histologic features of NASH in obesity surgery patients. METHODS: Subjects consisted of 238 patients who had a routine liver biopsy at the time of obesity surgery. Demographic and clinical variables pertaining to the metabolic syndrome were collected retrospectively. Liver biopsies were evaluated according to the scoring system proposed by the Nonalcoholic Steatohepatitis Clinical Research Network and NASH was defined as a NASH activity score > or =5. RESULTS: African Americans had lower rates of steatosis than non-Hispanic whites (P<0.001) and Hispanics (P=0.03). Among patients with steatosis, African Americans had lower rates of NASH than non-Hispanic whites (P=0.05) and Hispanics (P=0.02) and lower rates of fibrosis score > or =F2 than non-Hispanic whites (P=0.002) and Hispanics (P=0.04). Ethnic differences in rates of NAFLD, NASH, and fibrosis > or =F2 persisted when controlling for demographic variables and features of the metabolic syndrome in logistic regression analysis. There were no significant differences in steatosis, NASH, or fibrosis > or =F2 between non-Hispanic whites and Hispanics. CONCLUSIONS: African-American obesity surgery patients have a lower rate of NAFLD, NASH, and less severe fibrosis than non-Hispanic whites and Hispanics.

Liver Injury with Features Mimicking Autoimmune Hepatitis following the Use of Black Cohosh.

There are a growing number of cases detailing acute hepatic necrosis in patients taking black cohosh (Cimicifuga racemosa), an over-the-counter herbal supplement for management of menopausal symptoms. Our aim is to illustrate two cases of liver injury following the use of black cohosh characterized by histopathological features mimicking autoimmune hepatitis. Both patients reported black cohosh use for at least six months and had no evidence of another cause of liver disease. Their liver biopsies showed a component of centrilobular necrosis consistent with severe drug-induced liver injury. In addition, the biopsies showed characteristics of autoimmune-like liver injury with an interface hepatitis dominated by plasma cells. Although serum markers for autoimmune hepatitis were not particularly elevated, both patients responded to corticosteroids, supporting an immune-mediated component to the liver injury. Liver injury following the use of black cohosh should be included in the list of differential diagnoses for chronic hepatitis with features mimicking autoimmune hepatitis.

Diabetes and hepatic oxidative damage are associated with hepatitis C progression after liver transplantation.

BACKGROUND: Posttransplant diabetes mellitus (PTDM) is common after liver transplantation and was recently identified as a risk factor for hepatitis C progression. Increased levels of oxidative stress have been identified in diabetes and hepatitis C. The aim of this study was to evaluate the relationship among PTDM, oxidative damage in liver biopsy specimens, and fibrosis progression posttransplant. METHODS: Subjects consisted of 27 hepatitis C-infected liver transplant recipients who had liver biopsy specimens available from 49 protocol liver biopsies. Paraffin embedded liver tissue sections were stained for 8-hydroxy-2' deoxyguanosine (8-OHdG), an indicator of hydroxyl radical mediated tissue damage. The percentage of cells staining for 8-OHdG in a histologic section was categorized as high (>66%) versus low score (< or =66%). Fibrosis index was calculated as fibrosis score (0-4)/ years posttransplant. Time to bridging fibrosis or cirrhosis (F3-4) was compared as a function of PTDM and 8-OHdG score. RESULTS: Considering all 49 biopsies, fibrosis index was higher in cases with PTDM (P<0.001) and high 8-OHdG score (P=0.004). High 8-OHdG score was associated with PTDM (P=0.012). In time to event analyses, time to F3-4 was more rapid in patients with PTDM (P=0.02) and in those with high 8-OHdG scores (P<0.001). CONCLUSIONS: This study confirmed a relationship between PTDM and hepatitis C fibrosis progression and found that oxidative damage in liver biopsy specimens was associated with PTDM and more rapid development of advanced fibrosis.

Laboratory diagnosis and nonoperative management of biliary complications in living donor liver transplant patients.

BACKGROUND: Biliary complications associated with living donor liver transplantation (LDLT) remain a major problem. Information regarding biochemical abnormalities helpful for the diagnosis and the nonoperative management of such complications are limited. METHODS: Adult patients who underwent LDLT were retrospectively studied for biliary complications. Clinical findings and laboratory studies, that is, serum bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase were evaluated. Diagnostic percutaneous transhepatic cholangiogram or endoscopic retrograde cholangiogram followed by therapeutic interventions such as endoscopic sphincterotomy, stone extraction, balloon dilation, or stent placement were done as indicated. Follow-up data on clinical and biochemical outcomes were assessed. RESULTS: Among the first 29 patients who underwent LDLT, 7 patients (24%) developed biliary complications. Nonoperative treatment was undertaken through endoscopic retrograde cholangiogram in 4 cases, percutaneous transhepatic cholangiogram in 3 cases with a successful clinical outcome in 6 cases (84%). All patients with biliary stricture had a bilirubin level >1.5 mg/dL with 100% sensitivity. CONCLUSIONS: A number of patients developed biliary complications after LDLT. Nonoperative treatments were successful in most patients. Elevated serum bilirubin level may be helpful in the diagnosis of biliary stricture complicating LDLT.